Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas

Rapidly growing tumors often develop necrosis. In the present study the expression of vascular endothelial growth factor (VEGF) was investigated and compared to microvessel density and necrosis of renal cell carcinomas. In the tumor-host interface the microvessel density was significantly increased...

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Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2001-11, Vol.439 (5), p.645-652
Main Authors: HEMMERLEIN, Bernhard, KUGLER, Alexander, ÖZISIK, Rehyan, RINGERT, Rolf-Hermann, RADZUN, Heinz-Joachim, THELEN, Paul
Format: Article
Language:English
Subjects:
Antigens, Nuclear
Apoptosis
Biological and medical sciences
Carcinoma, Renal Cell - blood supply
Carcinoma, Renal Cell - metabolism
Carcinoma, Renal Cell - pathology
Cell Division
Endothelial Growth Factors - biosynthesis
Endothelial Growth Factors - genetics
Endothelium, Vascular - metabolism
Endothelium, Vascular - pathology
Humans
Immunohistochemistry
In Situ Hybridization
In Situ Nick-End Labeling
Kidney Neoplasms - blood supply
Kidney Neoplasms - metabolism
Kidney Neoplasms - pathology
Kidneys
Lymphokines - biosynthesis
Lymphokines - genetics
Matrix Metalloproteinase 2 - biosynthesis
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 9 - biosynthesis
Matrix Metalloproteinase 9 - genetics
Medical sciences
Microcirculation
Necrosis
Neovascularization, Pathologic - metabolism
Nephrology. Urinary tract diseases
Nuclear Proteins - analysis
Pericytes - metabolism
Pericytes - pathology
Platelet Endothelial Cell Adhesion Molecule-1 - analysis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
RNA, Neoplasm - analysis
Spheroids, Cellular - metabolism
Spheroids, Cellular - pathology
Tumor Cells, Cultured
Tumors of the urinary system
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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Summary:Rapidly growing tumors often develop necrosis. In the present study the expression of vascular endothelial growth factor (VEGF) was investigated and compared to microvessel density and necrosis of renal cell carcinomas. In the tumor-host interface the microvessel density was significantly increased compared to central tumor areas. Tumor necrosis was associated with a decrease of microvessel density and an increase of the VEGF protein expression within the perinecrotic rim. VEGF protein was focally upregulated in vital tumor tissue. An increase of the apoptotic rate of endothelia and vital tumor tissue in tumors with necrosis could not be detected. VEGF(121,165) mRNA was decreased in proliferatively active carcinomas compared to less proliferative tumors. Multicellular renal cell cancer spheroids as a model of chronic hypoxia developed central apoptosis but no necrosis. VEGF was upregulated in the spheroid. Tumor microvessels expressed matrix metalloproteinase -2 and -9 and an incomplete pericyte covering in comparison to tumor-free tissue indicating immature active angiogenesis. We conclude that highly proliferative renal cell carcinomas outgrow their vascular supply and develop chronic hypoxia inducing a decrease of proliferation and an increase of VEGF expression. However, chronic hypoxia does not cause significant necrosis or apoptosis. Tumor necrosis is more likely induced by acute hypoxia due to immature microvessels. Furthermore, VEGF expression associated with concomitant tumor necrosis may help identify renal cell carcinomas susceptible to antiangiogenic therapy.
ISSN:0945-6317
1432-2307
DOI:10.1007/s004280100464